NASHVILLE, Tennessee—Regimens that contain oxaliplatin(Drug information on oxaliplatin) (Eloxatin) as well as irintoecan (CPT-11, Camptosar) and fluorouracil(Drug information on fluorouracil) (5-FU)/ leucovorin have produced prolonged survival of 18 to 21 months in patients with advanced colorectal cancer and should be considered for first-line therapy, according to Mace L. Rothenberg, MD. Dr. Rothenberg, who is professor of medicine at Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, reviewed the current status of oxaliplatin-based regimens.
Oxaliplatin forms adducts that are bulkier and more hydrophobic than those formed by cisplatin(Drug information on cisplatin) and as a result may be more difficult to repair. Dr. Rothenberg said that oxaliplatin is also active against tumor cell lines that are resistant to cisplatin in vitro. "Colon cancer cell lines are not very sensitive to cisplatin or carboplatin(Drug information on carboplatin) (Paraplatin). Many are much more sensitive to oxaliplatin," Dr. Rothenberg said.
Improved Survival Not Initially Seen
Three European phase III trials of 5-FU/leucovorin with or without oxaliplatin showed a doubling or tripling of response rate and significant increases in progression-free survival, Dr. Rothenberg said, but this did not translate into an increase in overall survival. The US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee recommended in March 2000 against approval of oxaliplatin for first-line treatment of advanced colorectal cancer
"There is a requirement by the FDA that a therapy that adds toxicity must offset that toxicity with a tangible benefit to patients (ie, survival)," Dr. Rothenberg explained. "The committee also had knowledge of first-line irinotecan(Drug information on irinotecan) data, to be presented that same day, demonstrating a survival advantage in two phase III studies."
In analyzing why there was no improvement in survival despite improved time to progression, Dr. Rothenberg said that the trials might have been underpowered to detect a survival difference and might have been affected by subsequent therapy, including oxaliplatin that was administered to patients originally treated with 5-FU/leucovorin.
Shifted Strategy
